The binding of ligands to molecules on the surface of cells often results in the transduction of intracellular signals. Frequently, such binding initiates a complicated cascade of second messengers, the end result of which is either stimulatory or inhibitory to the cell. Ligand binding can modulate cellular homeostasis by altering, for example, the activation state, growth, or differentiation of cells, usually by modulating gene transcription.
Antibodies to many cellular receptors, other cell-associated molecules, and ligands, such as cytokines and other growth factors have been developed. Some of these antibodies stimulate signal transduction, while others block or inhibit the signals transduced by the binding of cognate ligands. Still other antibodies bind to specific populations of cells and, therefore, are useful in targeting or identifying such cells in vivo. e.g., for visualization using a detectable label or for killing by a cytotoxic drug.
The development of such antibodies for diagnostic or therapeutic use has often been hampered, however, by problems with half-life, effective dose at the target site, toxicity and the like. The development of antigen binding molecules and method of generating such antigen binding molecules having improved properties would be of great benefit in the development of diagnostics and therapeutics.